Paediatric Sepsis

1:15am: 3 year old female arrives at Triage with

HR 180, RR 35, looks tired. Has had URTI
symptoms for past couple of days.
1:25am: ICU/Paeds Reg called by ED doctor
saying can you come and have a look
1:35am:You make your first assessment

HR 180
Quiet, tired, opens eyes
Mod respiratory distress
Cap refill 4 seconds

WHAT DO YOU DO?

Why are we worried about it?

Still remains significant cause of morbidity and
mortality
5-30% of paediatric patients with sepsis will
develop septic shock
Mortality rates in septic shock are 20-30% (up
to 50% in some countries)

Recognition
Most people dont recognise shock
Resuscitation must be done in a proactive
time-sensitive manner
Every minute counts golden hour
Every hour without appropriate resuscitation
and restoration of blood pressure increases
mortality risk by 40%

How do we define it

Systemic Inflammatory Response Syndrome

Infection
Sepsis
Severe Sepsis
Septic Shock

Systemic Inflammatory Response

Syndrome
Presence of 2 of the following criteria:
Core Temp >38.5 or < 36 degrees
Mean HR > 2SD for age or persistent elevation
over 0.5-4hrs
If < 1yr old: bradycardia HR < 10th centile for
age
Mean RR > 2 SD above normal for age
Leucocyte abnormality

SEPSIS

SIRS in presence of suspected or proven

infection
Severe Sepsis

Sepsis + one of the following

CV organ dysfunction
ARDS
2 or more organ dysfunction
Septic Shock

Sepsis + CV organ dysfunction

Cardiovascular dysfunction
Despite >40ml/kg Isotonic fluid bolus in 1
hour:
Decrease in BP <5th centile for age
Need for vasoactive drug to maintain BP
2 of the following:

Unexplained metabolic acidosis

Increase lactate
Oliguria
Prolonged cap refill > 5 seconds
Core-peripheral temp gap >3 degrees

Risk factors for Sepsis in Children

< 1 year of age

Very low birthweight infants
Prematurity
Presence of underlying illness eg chronic lung,
cardiac conditions, malignancy
Co-morbidities
Boys
Genetic factors

What makes you suspect shock?

Clinical Manifestations

Fever
Increased HR
Increased RR
Altered mental state
Skin:

Hypoperfusion
Decreased capillary refill
Petechiae, purpura
Cool vs warm.

Cold Shock

Warm Shock

HR

Tachycardia

Tachycardia

Peripheries

Cool

Warm

Pulses

Difficult to palpate

Bounding

Skin

Mottled, pale

Flushed

Capillary refill

Prolonged

Blushing

Mental state

Altered

Altered

Urine

Oliguria

Oliguria

Blood Pressure in Children

This is main difference with adults.
Blood pressure does not fall in septic shock
until very late.
CO= HR x SV
HR in children much higher therefore BP
falling is late.
Pulse pressure is often useful
Normal: Diastolic BP > systolic BP.

Investigations
Basic bloods:
CBC, EUC, LFT, CMP, Coags, Glucose
Inflammatory markers: PCT, CRP
Acid- Base status
Venous or arterial blood gas:
Lactate
Base deficit

Investigations
Septic Work up
Urine, blood, sputum cultures
Viral cultures: throat, NPA, faeces,
Never do CSF in shocked patient
Imaging:
CXR, CT, MRI, PET scan, ECHO, Ultrasound

MANAGEMENT

General Principles
Early Recognition
Early and appropriate antimicrobials
Early and aggressive therapy to restore
balance between oxygen delivery and demand
Early and goal directed therapy

What is Goal Directed Therapy?

Based on studies in adults initially
Use fluid resuscitation, vasoactive infusions,
oxygen to aim to restore balance between
oxygen delivery and demand
Goals:

Capillary refill < 2 seconds

Urine ouptut > 1ml/kg/hr
Normal pulses
Improved mental state
Decreased lactate and base deficits
Perfusion pressures appropriate for age

O min

Recognise decreased mental status and perfusion

Maintain airway and establish access

5 min

Push 20mls/kg isotonic saline or colloid boluses up to and over

60mls/kg
Antimicrobials, Correct hypoglycemia and hypocalemia

15 min

Fluid Responsiveness

Observe in PICU

Fluid Refractory shock

Recognise decreased mental status and perfusion

Maintain airway and establish access
Vascular Access:
Only few minutes to be spent on obtaining IV access
Need to use IO if cant get access
May need to put 2 x IO in
Intubation + Ventilation
Clinical assessment of work of breathing , hypoventilation or impaired
mental state
Up to 40% of cardiac output is used for work of breathing
Volume loading and inotrope support is recommended before and during
intubation
Recommended: Ketamine, atropine and short acting neuromuscular
blocking agent.

Push 20mls/kg isotonic saline or colloid boluses up to and over

60mls/kg
Antimicrobials, Correct hypoglycemia and hypocalemia

Fluid Resuscitation:
Needs to be given as push
May need to give up to 200mls/kg
Give fluid until perfusion improves.

Which Fluids
Isotonic vs collloid
Most evidence extrapolated from adults
Wills et al
RCT of cystalloid vs colloid in children with dengue fever
No difference between the two groups.

15min

Fluid Refractory Shock

Begin dopamine or peripheral adrenaline

Establish central venous access
Establish arterial access

Titrate Adrenaline for cold shock and noradrenaline for

warm shock to normal MAP-CVP and SVC sats>70%

60 min

Catecholamine resistant shock

Catecholamine Resistant Shock

At Risk of adrenal insufficency give

hydrocortisone

Not at Risk - dont give

hydrocortisone

Normal Blood Pressure

Cold Shock
SVC < 70%

Low Blood Pressure

Cold Shock
SVC < 70%

Low Blood
Pressure
Warm Shock

Add vasodilator or
Type III PDE inhibitor

Titrate volume and

adrenaline

Titrate volume &

Noradrenaline
Consider
Vasopressin

ECMO

Drug

Dose

Comments

Dopamine

2-20mcg/kg/min

Historically 1st choice in kids

Alpha, beta and dopamine receptor
activation
Can be given peripherally

Dobutamine

5-10mcg/kg/min

Chronotropic as well as inotropic

Afterload reduction

Adrenaline

0.05- 1mcg/kg/min

Initially increases contractility/heart

rate
High doses increase PVR

Noradrenaline 0.05 1
mcg/kg/min

Vasopressor
Increases PVR

Milrinone

Phosphodiesterase inhibitor
Afterload reduction

0.250.75mcg/kg/min

Rivers et al, NEJM 2001

Single Centre , RCT in Emergency Department
Goal directed vs standard care in septic adults in
first 6 hours in ED
Goal directed therapy consisted of

CVP 8-12mmHg
MAP > 65mmHg
Urine output >0.5ml/kg/hour
ScVO2 > 70%

Showed significant decrease in mortality

Cristisms: control group had higher mortality rate
and benefits may be because group was
monitored more closely

Ceneviva et al, Pediatrics 1998

Single centre, 50 children
Used goal directed therapy : CI 3.3-6Lmin/m2
in children with fluid refractory shock
Mortality from sepsis decreased by 18% when
compared to 1985 study

De Oliveira ICM 2008

RCT , single centre
Use of 2002 guidelines with continous central
venous O2 saturation monitoring and therapy
directed to maintain ScVO2 > 70%
Mortality decreased from 39% to 12 %,
Number needed to treat 3.6

Brierley and Carcillo CCM 2009

Update of 2002 guidelines for goal directed
therapy
Look at all studies who had adopted 2002
guidelines and their success.
Reported studies that showed decrease in
mortality with adoption of 2002 guidelines.
New changes :
Inotrope via peripheral access
Fluid removal considered early

What about Hydrocortisone?

Controversial
Rational is that there is hypothalamic-pituitary
adrenal axis dyfunction in patients with septic
shock
Current recommendations:
If child is at risk of adrenal insufficency and remains in
shock should receive hydrocortisone
At risk defined as purpura fulminans, congenital
adrenal hyperplasia, recent steroid exposure,
hypothalamic/pituitary abnormality

Evidence Controversial
Annane D JAMA 2002
Multicentre , RCT looked at use of hydrocortisone and
fludrocortisone in septic shock.

Corticus Trial, NEJM 2008

Mutlicentre, RCT
Hydrocortisone vs placebo in septic shock
No significant difference in mortality
Many criticisms
Inadequate power
Selection bias

Evidence- paediatrics
No RCT in paediatric patients with sepsis
Markovitz : PCCM 2005
Retrospective cohort study , 6000 paediatric
patients
Systemic steriods associated with increased
mortality
But no control in place for severity of illness or for
dose.

Other treatment

Maintain Glucose control

Nutrition
Maintain Hb > 10g/dL
GI protection
Early CVVH

Activated Protein C
Inhibits factors Va and VIIIa prevent
generation of thrombin
Decreased inflammation through inhibition of
platelet activation, neutrophil recruitment
Initially had popularity as possible treatment
option in septic shock
Concern with it is risk of serious haemorrhage

RESOLVE Study, Lancet 2007

RCT, multicentre, international study in 477
children with severe sepsis.
Compared APC to placebo for 96 hrs
Primary end point: time to complete organ
failure resolution
Study stopped early as interim analysis
showed no benefit
More bleeding in APC group but not
significantly different

ECMO
Study published this month from RCH Melbourne

Looked at ECMO use in paediatric septic shock

96% had at least 3 organ failure and 35% had a cardiac arrest
prior to ECMO

23 patients with refractory septic shock received central

ECMO
17 (74%) patients survived to be discharged from hospital.